structure SMB Infrastructure Courses By www.ibm.com Published On :: 2008-05-23-05:00 IBM Business Partners can help their clients find new ways to solve a variety of infrastructure problems by attending one of the four new microcourses offered by SMB College. Full Article
structure Discover IBM Dynamic Infrastructure By www-200.ibm.com Published On :: 2009-04-02-14:00 Learn how IBM Business Partners can help their clients reduce costs, manage risks and improve service with Dynamic Infrastructure products, services and solutions. Full Article
structure Cooling Water Intake Structure Coalition v. EPA By feeds.findlaw.com Published On :: 2018-07-23T08:00:00+00:00 (United States Second Circuit) - Denied petitions for review of the U.S. Environmental Protection Agency's final rule related to cooling water intake structures. The petitioners in this case, a number of environmental conservation groups and industry associations, sought judicial review of an EPA rule promulgated under the Clean Water Act establishing requirements for cooling water intake structures, which are used by power plants and manufacturing facilities to extract water and dissipate waste heat. Denying the petitions, the Second Circuit concluded that the final rule was sufficiently supported by the factual record and that the EPA gave adequate notice of its rulemaking. Full Article Public Utilities Environmental Law Water Law
structure Mission Bay Alliance v. Office of Community Investment and Infrastructure By feeds.findlaw.com Published On :: 2016-11-29T08:00:00+00:00 (California Court of Appeal) - In an appeal from the trial court's denial of two consolidated petitions to set aside the certification of the environmental impact report and related permits for the construction of an arena to house the Golden State Warriors basketball team, as well as other events, and the construction of adjacent facilities, in the Mission Bay South redevelopment plan area of San Francisco, the trial court's judgment is affirmed where there is no merit to plaintiffs' objections to the sufficiency of the city's environmental analysis and its approval of the proposed project. Full Article Sports Law Environmental Law Government Law
structure Balfour Beatty Infrastructure, Inc. v. Mayor and City Council of Baltimore By feeds.findlaw.com Published On :: 2017-04-25T08:00:00+00:00 (United States Fourth Circuit) - In a construction company's suit against a city for breach of contract, alleging that the city unlawfully assessed liquidated damages against the company for failure to complete a construction project on time, the district court’s dismissal for lack of subject matter jurisdiction is affirmed where plaintiff is not excused from the normal requirement of administrative exhaustion under Maryland law. Full Article Government Contracts Construction Contracts
structure In re Border Infrastructure Environmental Litigation By feeds.findlaw.com Published On :: 2019-02-11T08:00:00+00:00 (United States Ninth Circuit) - Held that the U.S. Department of Homeland Security had the statutory authority to expedite construction of physical border barriers near San Diego and Calexico, California. The State of California and multiple environmental groups challenged the agency's 2017 authorization of these projects, which involved wall prototypes and tens of miles of replacement fencing. However, the Ninth Circuit affirmed summary judgment in favor of the federal government. Full Article Environmental Law Immigration Law Construction
structure In re Border Infrastructure Environmental Litigation By feeds.findlaw.com Published On :: 2019-02-11T08:00:00+00:00 (United States Ninth Circuit) - Held that the U.S. Department of Homeland Security had the statutory authority to expedite construction of physical border barriers near San Diego and Calexico, California. The State of California and multiple environmental groups challenged the agency's 2017 authorization of these projects, which involved wall prototypes and tens of miles of replacement fencing. However, the Ninth Circuit affirmed summary judgment in favor of the federal government. Full Article Environmental Law Immigration Law Construction
structure Existing and Emerging Highway Infrastructure Preservation, Maintenance, and Renewal Definitions, Practices, and Scenarios By www.trb.org Published On :: Thu, 23 Apr 2020 13:45:15 GMT The National Cooperative Highway Research Program's NCHRP Web-Only Document 272: Existing and Emerging Highway Infrastructure Preservation, Maintenance, and Renewal Definitions, Practices, and Scenarios provides appendices to NCHRP Report 750, Volume 7: Preservation, Maintenance, andRenewal of Highway Infrastructure . Full Article
structure Tenth International Conference on Structural Health Monitoring of Intelligent Infrastructure* By www.trb.org Published On :: Fri, 08 May 2020 04:00:44 GMT International Society for Structural Health Monitoring of Intelligent Infrastracture will host Tenth International Conference on Structural Health Monitoring of Intelligent Infrastructure on June 30 - July 2, 2021 in Porto, Portugal. TRB is pleased to cosponsor this event. The conference provides a forum for idea exchanges, knowledge sharing, and technology-need matchmaking in the global Structural Health Monitoring and Nondestructive Testing community. It serves as a unique venue to showcase U.S. and gl... Full Article
structure Improving AEDT Modeling for Aircraft Noise Reflection and Diffraction from Terrain and Manmade Structures By www.trb.org Published On :: Mon, 23 Dec 2019 06:32:32 GMT Barriers, berms, buildings, and natural terrain may affect the propagation of aircraft noise by shielding or reflecting sound energy. If terrain and manmade structures obstruct the line‐of‐sight between the source and the receiver, then sound energy will be attenuated at the receiver. This attenuation increases with the terrain and structures’ size and proximity to either the source or the receiver. If gaps exist in the terrain or structures, then the potential benefits of acoustical shielding will be su... Full Article http://www.trb.org/Resource.ashx?sn=cover_acrp_wod_44
structure Repairing and Maintaining Airport Parking Structures While in Use By www.trb.org Published On :: Thu, 13 Jun 2013 04:47:01 GMT TRB’s Airport Cooperative Research Program (ACRP) Synthesis 47: Repairing and Maintaining Airport Parking Structures While in Use provides information on developing and implementing successful maintenance and repair strategies for in-use airport parking structures that involve the least impact on the airport patrons, revenue stream, and facility operations. Full Article http://www.trb.org/Resource.ashx?sn=cover_acrp_syn_047copy
structure Featured Centennial Paper - TRB’s Role in Transportation Infrastructure Protection and Resilience By www.trb.org Published On :: Fri, 08 May 2020 06:39:14 GMT Standing Technical Committee on Critical Transportation Infrastructure got its start as the Task Force on Critical Transportation Infrastructure Security tied directly in response to the Presidential Decision Directive 63, Critical Infrastructure Protection (PPD-63). Soon after the task force was established, as a way to bring awareness to this topic, TRB published a special edition of TR News (211): Transportation Security: Protecting the System from Attack and Theft (November-December 2000). The editio... Full Article
structure Bone Structure By www.oglaf.com Published On :: Sun, 21 Jul 2019 00:00:00 +0000 Full Article
structure Three Paper Thursday: The role of intermediaries, platforms, and infrastructures in governing crime and abuse By www.lightbluetouchpaper.org Published On :: Thu, 09 Apr 2020 09:00:00 +0000 The platforms, providers, and infrastructures which together make up the contemporary Internet play an increasingly central role in the business of governing human societies. Although the software engineers, administrators, business professionals, and other staff working at these organisations may not have the institutional powers of state organisations such as law enforcement or the civil service, … Continue reading Three Paper Thursday: The role of intermediaries, platforms, and infrastructures in governing crime and abuse → Full Article Three Paper Thursday
structure IBM to Make up to US$5 Billion Available to Accelerate Smart Infrastructure Initiatives Around the World By www.ibm.com Published On :: Tue, 02 Jun 2009 11:42:46 GMT IBM announced today it is making up to €2.2 billion ($3 billion) available to finance IT initiatives in key economic stimulus projects in Europe and Asia-Pacific through IBM Global Financing, IBM’s lending and leasing business segment. Today’s announcement follows the availability of up to €1.5 billion ($2 billion) announced by IBM on April 30 to help jump start US economic stimulus programs. Full Article Global Financing
structure IBM Extends Infrastructure Services Relationship With Medicare of Australia for One Year By www.ibm.com Published On :: Wed, 22 Oct 2008 03:46:44 GMT IBM (NYSE: IBM) today announced it has signed a one-year extension to its contract with Australian government agency, Medicare, for the provision of IT infrastructure services. Full Article Healthcare and Life Sciences
structure IBM Extends Infrastructure Services Deal with Department of Health & Ageing for Four Years By www.ibm.com Published On :: Thu, 23 Dec 2010 08:20:32 GMT IBM Australia (NYSE: IBM) today announced a four-year extension to its contract with Australian government agency, Department of Health & Ageing, for the provision of IT infrastructure services. The deal includes a variation to the final year of the existing agreement, and has a total value of $109m over five years. Full Article Government
structure IBM positioned as the Leader in the Gartner Magic Quadrant for Data Center Outsourcing and Hybrid Infrastructure Managed Services, Asia Pacific By www.ibm.com Published On :: Mon, 22 Oct 2018 05:10:52 GMT IBM positioned as the Leader in the Gartner Magic Quadrant for Data Center Outsourcing and Hybrid Infrastructure Managed Services, Asia Pacific Full Article Global Technology Services
structure Level35 selects IBM Watson and Cloud to speed major infrastructure projects By www.ibm.com Published On :: Wed, 11 Oct 2017 05:19:57 GMT Melbourne-based start-up Level35 is using Watson, the cognitive computing platform developed by IBM (NYSE: IBM), and IBM Cloud to help public-sector project managers improve how they communicate within some of the largest government agencies in Australia. Full Article IBM Watson
structure Synergy Plus Wins IBM Beacon Award for Leadership in Optimizing IT Infrastructure By www.ibm.com Published On :: Wed, 28 May 2008 02:32:01 GMT Hyro Limited group company, Synergy Plus Pty Ltd (“Synergy”) has been named winner of the award for “Leadership in Optimizing IT Infrastructure” in the annual IBM Beacon Awards competition, honoring IBM Business Partners for their ingenuity, innovation, customer satisfaction and outstanding achievements in providing business solutions. Full Article Business partners
structure “It’s the embers, stupid!” CAL FIRE staff chief addresses structure loss; reducing wildfire risk in the wildland-urban interface By community.nfpa.org Published On :: Wed, 09 Aug 2017 12:54:24 PDT As most of us know, states across the U.S. can no longer rely on a defined fire season. This sobering truth is especially evident in California where the fire season is 70 days longer than it was 40 years ago, and fire ignitions in the state have greatly Full Article fire service wildfire wildfire prevention wildfire hazards wildfire risk wildfire hazard mitigation community risk reduction cal fire ce2017 defensible space wildfire embers
structure Scotland league restructure plans abandoned By www.rte.ie Published On :: Fri, 08 May 2020 20:51:18 +0000 Plans to restructure the league system in Scotland have broken down following a meeting of Scottish Premiership clubs. Full Article Soccer
structure Infrastructure Asset Program Analyst By www.engineer.net Published On :: Thu, 25 Jan 2018 00:00:00 UTC DUTIES: **All applications must be submitted by January 31, 2018, at http://www.mdc.mo.gov/about/jobs. **Any applications submitted through external sources will not be reviewed. Works as a member of the Infrastructure Asset Management Program Team and supports the Design and Development Divisi Full Article
structure Infrastructure Asset Program Specialist By www.engineer.net Published On :: Thu, 25 Jan 2018 00:00:00 UTC DUTIES: **All applications must be submitted by January 31, 2018, at http://www.mdc.mo.gov/about/jobs. **Any applications submitted through external sources will not be reviewed. Works as a member of the Infrastructure Asset Management Program Team and supports the Design and Development Divisi Full Article
structure Engineer III - Structures Inspection Program By www.engineer.net Published On :: Fri, 09 Feb 2018 00:00:00 UTC Mission: Engineer responsible for performing structure inspections in accordance with MetroLink's Structures Inspection Program, structural review of design calculations, plans, and specifications, design and construction oversight of structural repairs, providing engineering support as re Full Article
structure strataconf: As infrastructure gets simpler, interesting big data apps can emerge on BDAS, @Cloudera & other Hadoop distributions http://t.co/jaATalPL4P By twitter.com Published On :: Tue, 11 Jun 2013 16:17:47 +0000 strataconf: As infrastructure gets simpler, interesting big data apps can emerge on BDAS, @Cloudera & other Hadoop distributions http://t.co/jaATalPL4P Full Article
structure HPE and VMware Team Up on Composable Infrastructure, Hybrid Cloud By feedproxy.google.com Published On :: Wed, 30 Aug 2017 17:43:44 +0000 Full Article Cloud DevOps Hewlett Packard Enterprise VMware
structure Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections. Full Article
structure Zinc promotes liquid-liquid phase separation of tau protein [Protein Structure and Folding] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Tau is a microtubule-associated protein that plays a major role in Alzheimer's disease (AD) and other tauopathies. Recent reports indicate that, in the presence of crowding agents, tau can undergo liquid–liquid phase separation (LLPS), forming highly dynamic liquid droplets. Here, using recombinantly expressed proteins, turbidimetry, fluorescence microscopy imaging, and fluorescence recovery after photobleaching (FRAP) assays, we show that the divalent transition metal zinc strongly promotes this process, shifting the equilibrium phase boundary to lower protein or crowding agent concentrations. We observed no tau LLPS-promoting effect for any other divalent transition metal ions tested, including Mn2+, Fe2+, Co2+, Ni2+, and Cu2+. We also demonstrate that multiple zinc-binding sites on tau are involved in the LLPS-promoting effect and provide insights into the mechanism of this process. Zinc concentration is highly elevated in AD brains, and this metal ion is believed to be an important player in the pathogenesis of this disease. Thus, the present findings bring a new dimension to understanding the relationship between zinc homeostasis and the pathogenic process in AD and related neurodegenerative disorders. Full Article
structure The major subunit of widespread competence pili exhibits a novel and conserved type IV pilin fold [Protein Structure and Folding] By feedproxy.google.com Published On :: 2020-05-08T03:41:14-07:00 Type IV filaments (T4F), which are helical assemblies of type IV pilins, constitute a superfamily of filamentous nanomachines virtually ubiquitous in prokaryotes that mediate a wide variety of functions. The competence (Com) pilus is a widespread T4F, mediating DNA uptake (the first step in natural transformation) in bacteria with one membrane (monoderms), an important mechanism of horizontal gene transfer. Here, we report the results of genomic, phylogenetic, and structural analyses of ComGC, the major pilin subunit of Com pili. By performing a global comparative analysis, we show that Com pili genes are virtually ubiquitous in Bacilli, a major monoderm class of Firmicutes. This also revealed that ComGC displays extensive sequence conservation, defining a monophyletic group among type IV pilins. We further report ComGC solution structures from two naturally competent human pathogens, Streptococcus sanguinis (ComGCSS) and Streptococcus pneumoniae (ComGCSP), revealing that this pilin displays extensive structural conservation. Strikingly, ComGCSS and ComGCSP exhibit a novel type IV pilin fold that is purely helical. Results from homology modeling analyses suggest that the unusual structure of ComGC is compatible with helical filament assembly. Because ComGC displays such a widespread distribution, these results have implications for hundreds of monoderm species. Full Article
structure America's Coronavirus Response Is Shaped By Its Federal Structure By feedproxy.google.com Published On :: Mon, 16 Mar 2020 09:00:36 +0000 16 March 2020 Dr Leslie Vinjamuri Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme @londonvinjamuri Google Scholar The apparent capacity of centralized state authority to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. 2020-03-16-Coronavirus-America.jpg Harvard asked its students to move out of their dorms due to the coronavirus risk, with all classes moving online. Photo by Maddie Meyer/Getty Images. As coronavirus spreads across the globe, states grapple to find the ideal strategy for coping with the global pandemic. And, in China, Singapore, South Korea, the US, the UK, and Europe, divergent policies are a product of state capacity and legal authority, but they also reveal competing views about the optimal role of centralized state authority, federalism, and the private sector.Although it is too soon to know the longer-term effects, the apparent capacity of centralized state authority in China, South Korea and Singapore to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. America’s response is being shaped by its federal structure, a dynamic private sector, and a culture of civic engagement. In the three weeks since the first US case of coronavirus was confirmed, state leaders, public health institutions, corporations, universities and churches have been at the vanguard of the nation’s effort to mitigate its spread.Images of safety workers in hazmat suits disinfecting offices of multinational corporations and university campuses populate American Facebook pages. The contrast to the White House effort to manage the message, downplay, then rapidly escalate its estimation of the crisis is stark.Bewildering responseFor European onlookers, the absence of a clear and focused response from the White House is bewildering. By the time President Donald Trump declared a national emergency, several state emergencies had already been called, universities had shifted to online learning, and churches had begun to close.By contrast, in Italy, France, Spain and Germany, the state has led national efforts to shutter borders and schools. In the UK, schools are largely remaining open as Prime Minister Boris Johnson has declared a strategy defined by herd immunity, which hinges on exposing resilient populations to the virus.But America has never shared Europe’s conviction that the state must lead. The Center for Disease Control and Prevention, the leading national public health institute and a US federal agency, has attempted to set a benchmark for assessing the crisis and advising the nation. But in this instance, its response has been slowed due to faults in the initial tests it attempted to rollout. The Federal Reserve has moved early to cut interest rates and cut them again even further this week.But states were the real first movers in America’s response and have been using their authority to declare a state of emergency independent of the declaration of a national emergency. This has allowed states to mobilize critical resources, and to pressure cities into action. After several days delay and intense public pressure, New York Governor Andrew Cuomo forced New York City Mayor Bill de Blasio to close the city’s schools.Declarations of state emergencies by individual states have given corporations, universities and churches the freedom and legitimacy to move rapidly, and ahead of the federal government, to halt the spread in their communities.Washington state was the first to declare a state of emergency. Amazon, one of the state’s leading employers, quickly announced a halt to all international travel and, alongside Microsoft, donated $1million to a rapid-response Seattle-based emergency funds. States have nudged their corporations to be first movers in the sector’s coronavirus response. But corporations have willingly taken up the challenge, often getting ahead of state as well as federal action.Google moved rapidly to announce a move allowing employees to work from home after California declared a state of emergency. Facebook soon followed with an even more stringent policy, insisting employees work from home. Both companies have also met with World Health Organization (WHO) officials to talk about responses, and provided early funding for WHO’s Solidarity Response Fund set up in partnership with the UN Foundation and the Swiss Philanthropy Foundation.America’s leading research universities, uniquely positioned with in-house public health and legal expertise, have also been driving preventive efforts. Just days after Washington declared a state of emergency, the University of Washington became the first to announce an end to classroom teaching and move courses online. A similar pattern followed at Stanford, Harvard, Princeton and Columbia - each also following the declaration of a state of emergency.In addition, the decision by the Church of the Latter Day Saints to cancel its services worldwide followed Utah’s declaration of a state of emergency.The gaping hole in the US response has been the national government. President Trump’s declaration of a national emergency came late, and his decision to ban travel from Europe but - at least initially - exclude the UK, created uncertainty and concern that the White House response is as much driven by politics as evidence.This may soon change, as the House of Representatives has passed a COVID-19 response bill that the Senate will consider. These moves are vital to supporting state and private efforts to mobilize an effective response to a national and global crisis.Need for public oversightIn the absence of greater coordination and leadership from the centre, the US response will pale in comparison to China’s dramatic moves to halt the spread. The chaos across America’s airports shows the need for public oversight. As New York State Governor Cuomo pleaded for federal government support to build new hospitals, he said: ‘I can’t do it. You can’t leave it to the states.'When it comes to global pandemics, we may be discovering that authoritarian states can have a short-term advantage, but already Iran’s response demonstrates that this is not universally the case. Over time, the record across authoritarian states as they tackle the coronavirus will become more apparent, and it is likely to be mixed.Open societies remain essential. Prevention requires innovation, creativity, open sharing of information, and the ability to inspire and mobilize international cooperation. The state is certainly necessary, but it is not sufficient alone. Full Article
structure The heme-regulatory motifs of heme oxygenase-2 contribute to the transfer of heme to the catalytic site for degradation [Protein Structure and Folding] By feedproxy.google.com Published On :: 2020-04-17T00:06:05-07:00 Heme-regulatory motifs (HRMs) are present in many proteins that are involved in diverse biological functions. The C-terminal tail region of human heme oxygenase-2 (HO2) contains two HRMs whose cysteine residues form a disulfide bond; when reduced, these cysteines are available to bind Fe3+-heme. Heme binding to the HRMs occurs independently of the HO2 catalytic active site in the core of the protein, where heme binds with high affinity and is degraded to biliverdin. Here, we describe the reversible, protein-mediated transfer of heme between the HRMs and the HO2 core. Using hydrogen-deuterium exchange (HDX)-MS to monitor the dynamics of HO2 with and without Fe3+-heme bound to the HRMs and to the core, we detected conformational changes in the catalytic core only in one state of the catalytic cycle—when Fe3+-heme is bound to the HRMs and the core is in the apo state. These conformational changes were consistent with transfer of heme between binding sites. Indeed, we observed that HRM-bound Fe3+-heme is transferred to the apo-core either upon independent expression of the core and of a construct spanning the HRM-containing tail or after a single turnover of heme at the core. Moreover, we observed transfer of heme from the core to the HRMs and equilibration of heme between the core and HRMs. We therefore propose an Fe3+-heme transfer model in which HRM-bound heme is readily transferred to the catalytic site for degradation to facilitate turnover but can also equilibrate between the sites to maintain heme homeostasis. Full Article
structure Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability [Enzymology] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable, with T50 values of ∼30–40 °C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared with related extant forms, but they also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. Whereas extant human CYP1B1 has one molecule of α-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17β-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to its thermostability. Full Article
structure Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death By feedproxy.google.com Published On :: 2006-12-01 Nica M. BorradaileDec 1, 2006; 47:2726-2737Research Articles Full Article
structure The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function By feedproxy.google.com Published On :: 1992-02-01 JP SegrestFeb 1, 1992; 33:141-166Reviews Full Article
structure America's Coronavirus Response Is Shaped By Its Federal Structure By feedproxy.google.com Published On :: Mon, 16 Mar 2020 09:00:36 +0000 16 March 2020 Dr Leslie Vinjamuri Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme @londonvinjamuri Google Scholar The apparent capacity of centralized state authority to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. 2020-03-16-Coronavirus-America.jpg Harvard asked its students to move out of their dorms due to the coronavirus risk, with all classes moving online. Photo by Maddie Meyer/Getty Images. As coronavirus spreads across the globe, states grapple to find the ideal strategy for coping with the global pandemic. And, in China, Singapore, South Korea, the US, the UK, and Europe, divergent policies are a product of state capacity and legal authority, but they also reveal competing views about the optimal role of centralized state authority, federalism, and the private sector.Although it is too soon to know the longer-term effects, the apparent capacity of centralized state authority in China, South Korea and Singapore to respond effectively and rapidly is making headlines. In the United States, the opposite has been true. America’s response is being shaped by its federal structure, a dynamic private sector, and a culture of civic engagement. In the three weeks since the first US case of coronavirus was confirmed, state leaders, public health institutions, corporations, universities and churches have been at the vanguard of the nation’s effort to mitigate its spread.Images of safety workers in hazmat suits disinfecting offices of multinational corporations and university campuses populate American Facebook pages. The contrast to the White House effort to manage the message, downplay, then rapidly escalate its estimation of the crisis is stark.Bewildering responseFor European onlookers, the absence of a clear and focused response from the White House is bewildering. By the time President Donald Trump declared a national emergency, several state emergencies had already been called, universities had shifted to online learning, and churches had begun to close.By contrast, in Italy, France, Spain and Germany, the state has led national efforts to shutter borders and schools. In the UK, schools are largely remaining open as Prime Minister Boris Johnson has declared a strategy defined by herd immunity, which hinges on exposing resilient populations to the virus.But America has never shared Europe’s conviction that the state must lead. The Center for Disease Control and Prevention, the leading national public health institute and a US federal agency, has attempted to set a benchmark for assessing the crisis and advising the nation. But in this instance, its response has been slowed due to faults in the initial tests it attempted to rollout. The Federal Reserve has moved early to cut interest rates and cut them again even further this week.But states were the real first movers in America’s response and have been using their authority to declare a state of emergency independent of the declaration of a national emergency. This has allowed states to mobilize critical resources, and to pressure cities into action. After several days delay and intense public pressure, New York Governor Andrew Cuomo forced New York City Mayor Bill de Blasio to close the city’s schools.Declarations of state emergencies by individual states have given corporations, universities and churches the freedom and legitimacy to move rapidly, and ahead of the federal government, to halt the spread in their communities.Washington state was the first to declare a state of emergency. Amazon, one of the state’s leading employers, quickly announced a halt to all international travel and, alongside Microsoft, donated $1million to a rapid-response Seattle-based emergency funds. States have nudged their corporations to be first movers in the sector’s coronavirus response. But corporations have willingly taken up the challenge, often getting ahead of state as well as federal action.Google moved rapidly to announce a move allowing employees to work from home after California declared a state of emergency. Facebook soon followed with an even more stringent policy, insisting employees work from home. Both companies have also met with World Health Organization (WHO) officials to talk about responses, and provided early funding for WHO’s Solidarity Response Fund set up in partnership with the UN Foundation and the Swiss Philanthropy Foundation.America’s leading research universities, uniquely positioned with in-house public health and legal expertise, have also been driving preventive efforts. Just days after Washington declared a state of emergency, the University of Washington became the first to announce an end to classroom teaching and move courses online. A similar pattern followed at Stanford, Harvard, Princeton and Columbia - each also following the declaration of a state of emergency.In addition, the decision by the Church of the Latter Day Saints to cancel its services worldwide followed Utah’s declaration of a state of emergency.The gaping hole in the US response has been the national government. President Trump’s declaration of a national emergency came late, and his decision to ban travel from Europe but - at least initially - exclude the UK, created uncertainty and concern that the White House response is as much driven by politics as evidence.This may soon change, as the House of Representatives has passed a COVID-19 response bill that the Senate will consider. These moves are vital to supporting state and private efforts to mobilize an effective response to a national and global crisis.Need for public oversightIn the absence of greater coordination and leadership from the centre, the US response will pale in comparison to China’s dramatic moves to halt the spread. The chaos across America’s airports shows the need for public oversight. As New York State Governor Cuomo pleaded for federal government support to build new hospitals, he said: ‘I can’t do it. You can’t leave it to the states.'When it comes to global pandemics, we may be discovering that authoritarian states can have a short-term advantage, but already Iran’s response demonstrates that this is not universally the case. Over time, the record across authoritarian states as they tackle the coronavirus will become more apparent, and it is likely to be mixed.Open societies remain essential. Prevention requires innovation, creativity, open sharing of information, and the ability to inspire and mobilize international cooperation. The state is certainly necessary, but it is not sufficient alone. Full Article
structure Undercurrents: Episode 33 - Chinese Millennials, and Attacks on Infrastructure in Gaza By feedproxy.google.com Published On :: Thu, 16 May 2019 00:00:00 +0100 Full Article
structure X-ray structures of catalytic intermediates of cytochrome c oxidase provide insights into its O2 activation and unidirectional proton-pump mechanisms [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition. Full Article
structure Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections. Full Article
structure X-ray structures of catalytic intermediates of cytochrome c oxidase provide insights into its O2 activation and unidirectional proton-pump mechanisms [Molecular Biophysics] By feedproxy.google.com Published On :: 2020-04-24T06:08:45-07:00 Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition. Full Article
structure CBD News: Statement by Mr. Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of the World Green Roof Infrastructure Congress, 20 October, Toronto, Canada. By www.cbd.int Published On :: Tue, 20 Oct 2009 00:00:00 GMT Full Article
structure A characterization of the standard smooth structure of ????3 surface By www.ams.org Published On :: Thu, 02 Apr 2020 13:59 EDT Weimin Chen Proc. Amer. Math. Soc. 148 (2020), 2707-2716. Abstract, references and article information Full Article
structure Structures of the MHC-I molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope [Protein Structure and Folding] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8+ T-cell–mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I–β2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV–PA123–130. We determined the structure of the BF2*1501–PA123–130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA123–130 epitope in the chicken B15 lineage. Conformational characteristics of the PA123–130 epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8+ T cells specific for the HPAIV–PA123–130 epitope in peptide-immunized chickens indicated that a repertoire of CD8+ T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA123–130 epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens. Full Article
structure Inter-{alpha}-inhibitor heavy chain-1 has an integrin-like 3D structure mediating immune regulatory activities and matrix stabilization during ovulation [Glycobiology and Extracellular Matrices] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Inter-α-inhibitor is a proteoglycan essential for mammalian reproduction and also plays a less well-characterized role in inflammation. It comprises two homologous “heavy chains” (HC1 and HC2) covalently attached to chondroitin sulfate on the bikunin core protein. Before ovulation, HCs are transferred onto the polysaccharide hyaluronan (HA) to form covalent HC·HA complexes, thereby stabilizing an extracellular matrix around the oocyte required for fertilization. Additionally, such complexes form during inflammatory processes and mediate leukocyte adhesion in the synovial fluids of arthritis patients and protect against sepsis. Here using X-ray crystallography, we show that human HC1 has a structure similar to integrin β-chains, with a von Willebrand factor A domain containing a functional metal ion-dependent adhesion site (MIDAS) and an associated hybrid domain. A comparison of the WT protein and a variant with an impaired MIDAS (but otherwise structurally identical) by small-angle X-ray scattering and analytical ultracentrifugation revealed that HC1 self-associates in a cation-dependent manner, providing a mechanism for HC·HA cross-linking and matrix stabilization. Surprisingly, unlike integrins, HC1 interacted with RGD-containing ligands, such as fibronectin, vitronectin, and the latency-associated peptides of transforming growth factor β, in a MIDAS/cation-independent manner. However, HC1 utilizes its MIDAS motif to bind to and inhibit the cleavage of complement C3, and small-angle X-ray scattering–based modeling indicates that this occurs through the inhibition of the alternative pathway C3 convertase. These findings provide detailed structural and functional insights into HC1 as a regulator of innate immunity and further elucidate the role of HC·HA complexes in inflammation and ovulation. Full Article
structure The heme-regulatory motifs of heme oxygenase-2 contribute to the transfer of heme to the catalytic site for degradation [Protein Structure and Folding] By www.jbc.org Published On :: 2020-04-17T00:06:05-07:00 Heme-regulatory motifs (HRMs) are present in many proteins that are involved in diverse biological functions. The C-terminal tail region of human heme oxygenase-2 (HO2) contains two HRMs whose cysteine residues form a disulfide bond; when reduced, these cysteines are available to bind Fe3+-heme. Heme binding to the HRMs occurs independently of the HO2 catalytic active site in the core of the protein, where heme binds with high affinity and is degraded to biliverdin. Here, we describe the reversible, protein-mediated transfer of heme between the HRMs and the HO2 core. Using hydrogen-deuterium exchange (HDX)-MS to monitor the dynamics of HO2 with and without Fe3+-heme bound to the HRMs and to the core, we detected conformational changes in the catalytic core only in one state of the catalytic cycle—when Fe3+-heme is bound to the HRMs and the core is in the apo state. These conformational changes were consistent with transfer of heme between binding sites. Indeed, we observed that HRM-bound Fe3+-heme is transferred to the apo-core either upon independent expression of the core and of a construct spanning the HRM-containing tail or after a single turnover of heme at the core. Moreover, we observed transfer of heme from the core to the HRMs and equilibration of heme between the core and HRMs. We therefore propose an Fe3+-heme transfer model in which HRM-bound heme is readily transferred to the catalytic site for degradation to facilitate turnover but can also equilibrate between the sites to maintain heme homeostasis. Full Article
structure X-ray structures of catalytic intermediates of cytochrome c oxidase provide insights into its O2 activation and unidirectional proton-pump mechanisms [Molecular Biophysics] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition. Full Article
structure Structural insight into the recognition of pathogen-derived phosphoglycolipids by C-type lectin receptor DCAR [Protein Structure and Folding] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 The C-type lectin receptors (CLRs) form a family of pattern recognition receptors that recognize numerous pathogens, such as bacteria and fungi, and trigger innate immune responses. The extracellular carbohydrate-recognition domain (CRD) of CLRs forms a globular structure that can coordinate a Ca2+ ion, allowing receptor interactions with sugar-containing ligands. Although well-conserved, the CRD fold can also display differences that directly affect the specificity of the receptors for their ligands. Here, we report crystal structures at 1.8–2.3 Å resolutions of the CRD of murine dendritic cell-immunoactivating receptor (DCAR, or Clec4b1), the CLR that binds phosphoglycolipids such as acylated phosphatidyl-myo-inositol mannosides (AcPIMs) of mycobacteria. Using mutagenesis analysis, we identified critical residues, Ala136 and Gln198, on the surface surrounding the ligand-binding site of DCAR, as well as an atypical Ca2+-binding motif (Glu-Pro-Ser/EPS168–170). By chemically synthesizing a water-soluble ligand analog, inositol-monophosphate dimannose (IPM2), we confirmed the direct interaction of DCAR with the polar moiety of AcPIMs by biolayer interferometry and co-crystallization approaches. We also observed a hydrophobic groove extending from the ligand-binding site that is in a suitable position to interact with the lipid portion of whole AcPIMs. These results suggest that the hydroxyl group-binding ability and hydrophobic groove of DCAR mediate its specific binding to pathogen-derived phosphoglycolipids such as mycobacterial AcPIMs. Full Article
structure Structure of an ancestral mammalian family 1B1 cytochrome P450 with increased thermostability [Enzymology] By www.jbc.org Published On :: 2020-04-24T06:08:45-07:00 Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable, with T50 values of ∼30–40 °C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared with related extant forms, but they also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. Whereas extant human CYP1B1 has one molecule of α-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17β-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to its thermostability. Full Article
structure Correction: Comparative structure-function analysis of bromodomain and extraterminal motif (BET) proteins in a gene-complementation system. [Additions and Corrections] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 VOLUME 295 (2020) PAGES 1898–1914Yichen Zhong's name was misspelled. The correct spelling is shown above. Full Article
structure Structure-based discovery of a small-molecule inhibitor of methicillin-resistant Staphylococcus aureus virulence [Molecular Biophysics] By www.jbc.org Published On :: 2020-05-01T00:06:09-07:00 The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections. Full Article